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PubMed1984

Hydrogen evolution by strictly aerobic hydrogen bacteria under anaerobic conditions.

When strains and mutants of the strictly aerobic hydrogen-oxidizing bacterium Alcaligenes eutrophus are grown heterotrophically on gluconate or fructose and are subsequently exposed to anaerobic conditions in the presence of the organic substrates, molecular hydrogen is evolved. Hydrogen evolution started immediately after the suspension was flushed with nitrogen, reached maximum rates of 70 to 100 mumol of H2 per h per g of protein, and continued with slowly decreasing rates for at least 18 h. The addition of oxygen to an H2-evolving culture, as well as the addition of nitrate to cells (which had formed the dissimilatory nitrate reductase system during the preceding growth), caused immediate cessation of hydrogen evolution. Formate is not the source of H2 evolution. The rates of H2 evolution with formate as the substrate were lower than those with gluconate. The formate hydrogenlyase system was not detectable in intact cells or crude cell extracts. Rather the cytoplasmic, NAD-reducing hydrogenase is involved by catalyzing the release of excessive reducing equivalents under anaerobic conditions in the absence of suitable electron acceptors. This conclusion is based on the following experimental results. H2 is formed only by cells which had synthesized the hydrogenases during growth. Mutants lacking the membrane-bound hydrogenase were still able to evolve H2. Mutants lacking the NAD-reducing or both hydrogenases were unable to evolve H2.

Aerobiosis↗

PubMed1981

Variability of electrocardiographic and enzyme evolution of myocardial infarction in man.

We have studied the time course of development of ST segment elevation, R wave loss, and Q wave development in 41 patients using 35 lead praecordial mapping or 12 lead electrocardiograms in those with anterior and inferior infarcts, respectively. The first recording was at a mean time of six hours after the onset of pain; subsequent records were taken every eight hours for 24 hours, every 12 hours for the second day, and every day thereafter. Serial CK MB estimates were obtained at every four hours for the first 72 hours. There was good agreement in the time course between the electrocardiogram and enzyme evolution. Forty-one per cent of patients showed rapid infarction with R wave and Q wave evolution complete within 12 hours of pain and accompanied by a short duration of enzyme release (mean = 19.30 hours). Fifty-nine per cent of patients showed more prolonged infarction with longer R wave and Q wave evolution and enzyme release (mean = 30 hours). Four patients also showed delayed reinfarction. ST segment elevation was maximal at six hours in the whole group and was significantly lower thereafter. Patients with rapid infarction showed high initial ST segment elevation which decreased promptly compared with those with prolonged infarction, who showed moderate but more persistent ST segment elevation. This study shows the variability in the time course of the electrocardiogram and enzyme evolution after myocardial infarction in man.

Aged↗

PubMed2004

Fractal characterization of bpn weights evolution.

Training methodology of the Back Propagation Network (BPN) is well documented. One aspect of BPN that requires investigation is whether or not the BPN would get trained for a given training data set and architecture. In this paper the behavior of the BPN is analyzed during its training phase considering convergent and divergent training data sets. Evolution of the weights during the training phase was monitored for the purpose of analysis. The evolution of weights was plotted as return map and was characterized by means of fractal dimension. This fractal dimensional analysis of the weight evolution trajectories is used to provide a new insight to understand the behavior of BPN and dynamics in the evolution of weights.

Algorithms↗

PubMed2025

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy. We also uncover a co-evolution between the tumor and the T cell repertoire, as well as a longitudinal shift in the TME from an anti-tumor to an immunosuppressive state, linked to the acquisition of recurrently late ccRCC drivers 9p loss and SETD2 mutations. Our study reveals clinically-relevant and hitherto underappreciated non-genetic evolution patterns in ccRCC.

Journal Article↗

PubMed2002

Patterns of karyotype evolution in complexes of sibling species within three genera of African murid rodents inferred from the comparison of cytogenetic and molecular data.

Here we report on the analysis of three rodent sibling species complexes belonging to the African genera Arvicanthis, Acomys and Mastomys. Using cytogenetic and molecular approaches we set out to investigate how karyotype and molecular evolution are linked in these muroid sibling species and, in particular, to what extent chromosomal changes are relevant to cladogenic events inferred from molecular data. The study revealed that each complex is characterized by a distinct pattern of karyotype evolution (karyotypic orthoselection), and a specific mutation rate. However we found that the general pattern may be considerably modified in the course of evolution within the same species complex (Arvicanthis, Acomys). This observation suggests that karyotypic orthoselection documented in numerous groups is not so much a reflection of selection of a definite type of chromosomal mutation, as suggested by the classical concept, but is due to genome structure of a given species. In particular, karyotypic change appears related to the quantity and chromosomal location of repeated sequences. The congruence between the chromosomal and molecular data shows that chromosomal changes are often valuable phylogenetic characters (Arvicanthis and Mastomys, but not Acomys). However, most importantly the approach underscores the value of incorporating both in order to gain a better understanding of complex patterns of evolution. Moreover, the fact that every cladogenetic event in Mastomys is supported by two pericentric inversions allowed us to hypothesize that genetic differentiation is initiated by the suppression of recombination within inverted segments, and that the accumulation of multiple pericentric inversions reinforces genetic isolation leading to subsequent speciation. Finally, the low sequence divergences distinguishing karyotypically distinct sibling species within Arvicanthis and Mastomys emphasizes the power of combining cytogenetic and molecular approaches for the characterization of unrecognized components of biodiversity.

Africa South of the Sahara↗

PubMed2005

Differences in ischemic lesion evolution in different rat strains using diffusion and perfusion imaging.

BACKGROUND AND PURPOSE: Interstrain differences in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental stroke research. We investigated, in 2 commonly used rat strains (Sprague-Dawley [SD] and Wistar-Kyoto [WK]), the spatiotemporal evolution of ischemia after permanent suture MCAO using diffusion and perfusion imaging. METHODS: Serial measurements of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) were performed up to 210 min after MCAO. Lesion volumes were calculated by using previously established viability thresholds and correlated with infarct volume defined by 2,3,5-triphenyltetrazolium chloride staining 24 hours after MCAO. RESULTS: While the ADC-derived lesion volume increased rapidly during the first 120 min after MCAO and essentially stopped growing after 3 hours in SD rats, ADC lesion in WK rats increased progressively during the entire 210-min period and was significantly smaller at all time points (P<0.05). The abnormal perfusion volume correlated highly with the TTC-defined infarct size in both groups. In WK rats, the abnormal perfusion volume was significantly larger than the abnormal diffusion volume up to 90 min after MCAO (P<0.001), whereas the diffusion/perfusion mismatch was significant (P<0.001) only at 45 min in SD rats. ADC-CBF scatterplots analysis revealed a slower and less robust ADC decline over time in WK rats in pixels with severe (<20% of normal) and moderate (21 to 40% of normal) CBF reduction. CONCLUSIONS: This study demonstrated substantial differences in acute ischemic lesion evolution between SD and WK rats. These interstrain variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.

Animals↗

PubMed1988

Longitudinal evolution of individuals having appealed their committal to the C.A.S.

The longitudinal evolution of 66 patients admitted between 1976 and 1986 at the Centre Hospitalier Robert-Giffard, and who have appealed their case before the Commission des Affaires Sociales (C.A.S.) was studied. After a review of the literature, the authors compare the evolution of the patients whose appeal was accepted and who left the hospital against medical advice to those individuals whose appeal was rejected. The authors wanted to see if the first group of patients had a less favourable short-term and medium term evolution. From a study of the files and of the case notes prepared by the physicians for the C.A.S. hearings, the authors draw a profile of the typical individual of this group and they study the influence of 16 factors of dangerousness on the Commission's decisions. The results show that the short and medium term evolution of the patients who have appealed their case before the Commission does not differ significantly in the area of dangerousness, whether their appeal was accepted or rejected. However, the length of stay of those patients who had to remain in hospital was significantly longer and that may be the reason why the period of time between their discharge and their re-hospitalization was afterwards much longer. In light of these results, the authors comment on the importance given by the Commission to the legalistic rather than therapeutic aspects of cases.

Adult↗

PubMed2003

Clonal evolution and lack of cytogenetic response are adverse prognostic factors for hematologic relapse of chronic phase CML patients treated with imatinib mesylate.

We followed 141 patients treated with imatinib mesylate (> 300 mg) for chronicphase chronic myelogenous leukemia (CML) following failure of treatment with interferon. During 12 months from the start of imatinib mesylate treatment, 96.5% achieved a complete hematologic response, 47.0% achieved a major cytogenetic response, and 32.4% achieved a complete cytogenetic response. The proportion of patients with hematologic relapse was 10.9% at 12 months and 14.6% at 18 months. In a univariate Cox regression analysis, the only pretreatment characteristics that correlated with an increased risk of hematologic relapse were hemoglobin level less than 120 g/L (12 g/dL) (P =.02), increased bands in the peripheral blood (P =.01), and clonal evolution (P <.0001). In a multivariate analysis, an elevated platelet count (P =.03) and clonal evolution (P <.0001) were the only significant factors for hematologic relapse. During treatment, the absence of a major cytogenetic response within the first 6 months also significantly correlated with relapse (P =.03). Notably, patients failing to achieve a major cytogenetic response by 6 months had a significantly higher rate of hematologic relapse (27%) compared with those who achieved a major cytogenetic response by 6 months (3%), and patients with clonal evolution had a significantly higher risk of hematologic relapse (50%) than those without clonal evolution (9%).

Adult↗

PubMed2002

P2X7 receptor expression in evolutive and indolent forms of chronic B lymphocytic leukemia.

Human leukocytes express a receptor for extracellular nucleotides, named P2X7R, that in lymphocytes can either mediate cell death or proliferation, depending on the level of activation. The authors have investigated P2X7R expression and function in 21 patients affected by B-cell chronic lymphocytic leukemia, 13 with an evolutive and 8 with an indolent variant of the disease. Resting cytoplasmic Ca++ concentration was significantly higher in lymphocytes from patients with the evolutive compared with indolent variant. Furthermore, in the former, P2X7R stimulation triggered a Ca++ influx significantly larger. Higher Ca++ influx correlated with an increased P2X7R expression in the lymphocytes from patients with the evolutive form. Finally, incubation in the presence of extracellular adenosine triphosphate decreased spontaneous proliferation of lymphocytes from patients affected with the evolutive variant but had no effects on lymphocytes from patients with the indolent form. These results suggest that expression and function of P2X7R may correlate with the severity of B-cell chronic lymphocytic leukemia.

Adenosine Triphosphate↗

PubMed2006

The orthology of HLA-E and H2-Qa1 is hidden by their concerted evolution with other MHC class I molecules.

BACKGROUND: Whether MHC molecules undergo concerted evolution or not has been the subject of a long-standing debate. RESULTS: By comparing sequences of eight functional homologues of HLA-E from primates and rodents with those of MHC class Ia molecules from the same eight species, we find that different portions of MHC class I molecules undergo different patterns of evolution. By focusing our analyses sequentially on these various portions, we have obtained clear evidence for concerted evolution of MHC class I molecules, suggesting the occurrence of extensive interallelic and intergenic exchanges. Intra-species homogenisation of sequences is particularly noticeable at the level of exon 4, which codes for the alpha3 domain, but our results suggest that homogenisation also concerns certain residues of the alpha1-alpha2 codomain that lie outside the antigen recognition site. CONCLUSION: A model is presented in which Darwinian selective pressures due to pathogens could, at the same time, favour diversification of MHC class Ia molecules and promote concerted evolution of separate loci by spreading advantageous motifs arising by mutations in individual MHC molecules to other alleles and to other loci of the MHC region. This would also allow MHC molecules to co-evolve with the proteins with which they interact to fulfil their functions of antigen presentation and regulation of NK cell activity. One of the raisons d'être of the MHC may therefore be to favour at the same time both diversification of MHC class Ia molecules and homogenisation of the whole pool of MHC class I molecules (Ia and Ib) involved in antigen presentation. REVIEWERS: This article was reviewed by Stephan Beck, Lutz Walter and Pierre Pontarotti.

Journal Article↗

PubMed2001

The stochastic evolution of catalysts in spatially resolved molecular systems.

A fully stochastic chemical modelling technique is derived which describes the influence of spatial separation and discrete population size on the evolutionary stability of coupled amplification in biopolymers. The model is analytically tractable for an infinite-dimensional space (simplex geometry), which also provides insight into evolution in normal Euclidean space. The results are compared with stochastic simulations describing the co-evolution of combinatorial families of molecular sequences both in the simplex geometry and in lower (one, two and three) space dimensions. They demonstrate analytically the generic limits which exploitation place on co-evolving multi-component amplification systems. In particular, there is an optimal diffusion (or migration) coefficient for cooperative amplification and minimal and maximal threshold values for stable cooperation. Over a bounded range of diffusion rates, the model also exhibits stable limit cycles. Furthermore, the co-operatively coupled system has a maximum tolerable error rate at intermediate rates of diffusion. A tractable model is thereby established which demonstrates that spatial effects can stabilize catalytic biological information. The analytic behaviour in infinite-dimensional simplex space is seen to provide a reasonable guide to the spatial dependence of the error threshold in physical space. Nanoscale possibilities for the evolution of catalysis on the basis of the model are outlined. We denote the modelling technique by PRESS, Probability Reduced Evolution of Spatially-discrete Species.

Catalysis↗

PubMedDate not supplied

Evolutive behavior towards cardiomyopathy of treated (nifurtimox or benznidazole) and untreated chronic chagasic patients.

The aim of this work was to compare the evolution of chronic chagasic untreated patients (UTPs) with that of benznidazole or nifurtimox-treated patients (TPs). A longitudinal study from a low endemic area (Santa Fe city, Argentina) was performed during an average period of 14 years. Serological and parasitological analyses with clinical exams, ECG and X-chest ray were carried out. At the onset, 19/198 infected patients showed chagasic cardiomyopathy (CrChM) while 179 were asymptomatic. In this latter group the frequency of CrChM during the follow-up was lower in TPs compared with UTPs (3.2% vs 7%). Within the CrChM group, 2/5 TPs showed aggravated myopathy whereas this happened in 9/14 UTPs. Comparing the clinical evolution of all patients, 5.9% of TPs and 13% of UTPs had unfavourable evolution, but the difference is not statistically relevant. Serological titers were assessed by IIF. Titers equal to or lower than 1/64 were obtained in 86% of the TPs, but only in 38% of UTPs. The differences were statistically significant (geometric mean: 49.36 vs. 98.2). Antiparasitic assessment of the drugs (xenodiagnosis) proved to be effective. The low sensitivity in chronic chagasic patients must be born in mind. Despite treated patients showed a better clinical evolution and lower antibody levels than untreated ones, it is necessary to carry on doing research in order to improve therapeutic guidelines, according to the risk/benefit equation and based on scientific and ethical principles.

Adolescent↗

PubMedDate not supplied

[The evolution of chronic chagasic cardiopathy. I. The influence of parasitemia].

During eight years (1982-1990) the evolution of chronic chagasic cardiopathy and its relation to parasitemia was evaluated in 279 patients, 85 men and 194 women, studied by resting electrocardiography and xenodiagnosis. All patients were residents in Virgem da Lapa, State of Minas Gerais, Brazil and their ages varied from 7 to 76 years (average 42.6 y). According to the results of the electrocardiograms the evolution of chagasic cardiopathy was classified as a) unchanged--when there was no change of the initial pattern off the ECG, b) progressive--when there was deterioration of the ECG pattern and c) regressive-when there was normalization or regression of the ECG alterations. Regarding xenodiagnosis 120 were considered with positive parasitemia, one or more xenodiagnoses positive, and 159 with negative parasitemia--all xenodiagnoses negative. The results showed: a) chagasic cardiopathy unchanged in 172 (61.6%) patients, b) progressive in 99 (35.5%) patients and c) regressive in 8 (2.9%). There was no relation between the evolution of chagasic cardiopathy and parasitemia. Independent from parasitemia, the cardiopathy was progressive according to the age of the patients and significantly greater in males. In conclusion we can state that evolution of chronic chagasic cardiopathy is associated with the age and with the male sex, but not with parasitemia, and this may suggest that parasitemia is not related to the development of the chronic chagasic cardiopathy.

Adolescent↗

PubMed2005

External aggression to the limb as a predictive factor in the evolution of patients undergoing arterial revascularization.

PURPOSE: A variety of predictive factors for the evolution of arterial grafts in patients with critical ischemia have been well defined in clinical studies, including diabetes mellitus, dialytic renal insufficiency, smoking, and distal arterial runoff. The goal of this study was to determine whether patients with critical ischemia undergoing arterial reconstruction in which ischemic lesions appeared spontaneously, compared to those in which the ischemic lesion appeared following an external aggression to the limb present different patterns of evolution. METHODS: From February 2002 to January 2004, 100 patients undergoing infra-inguinal arterial reconstruction were followed. They were divided into 2 groups: 1) the spontaneous group (n = 52), comprising individuals presenting with ischemic lesions of spontaneous origin and 2) the external aggression to the limb group (n = 48), comprising individuals for which an external causal mechanism for the appearance of the ischemic lesion was identified. The variables analyzed were limb salvage and graft functioning rates. RESULTS: Patients with spontaneous lesions had rates of limb salvage and graft functioning significantly lower than those for patients with lesions that were secondary to external aggression (42.3% versus 87.5%, respectively for both outcomes; P <.001). CONCLUSIONS: The absence of an external aggression as a contributing factor to a critical ischemic lesion in the lower limb may result in a poorer evolution of both graft function and limb salvage following arterial revascularization. However, this factor is not expected to directly influence the case conduct, since almost half of the patients without evident external aggression had good graft functioning and limb salvage. This prognostic factor should be used just as all others are, i.e., to give patients and doctors a better idea of the possible evolution in such cases.

Amputation, Surgical↗

PubMed2005

Primate beta-defensins--structure, function and evolution.

Host defense peptides (HDPs) are endogenous antibiotics that play a multifunctional role in the innate immunity of mammals. Among these, beta-defensins contribute to mucosal and epithelial defense, also acting as signal molecules for cellular components of innate and adaptive immunity. Numerous members of this family have been identified in mammalian and avian species, and genomic studies in human and mouse indicate a considerable complexity in their gene organization. Recent reports on the evolution of primate and rodent members of this family indicate quite a complex pattern of variation. In this review we briefly discuss the evolution of mammalian beta-defensins in relation to other types of defensins, and then concentrate on the evolution of beta-defensins 1 to 4 in primates. In particular, the surprisingly varied patterns of evolution, which range from neutral or weakly purifying, to positive selection to a high level of conservation are analyzed in terms of possible genetics, structural or functional implications, as well as to observed variations on the antimicrobial activity in vitro. The role of polymorphisms in the genes encoding for these host defense peptides in determining susceptibility to human diseases are also briefly considered.

Amino Acid Sequence↗

PubMed2006

Drug evolution concept in drug design: 2. Chimera method.

The drug evolution method represents a novel approach towards efficient rational drug design by implementing the drug evolution concept to the creation and development of general chemical libraries with the purpose of allowing the identification of drug candidates with improved odds and lesser costs than the traditional drug design strategies. As another example of successful translation of the biological evolution into chemical evolution, the chimera method comprises the grafting of selected building blocks, identified through a basic search within a drug library, onto the same substitution sites on a rationally chosen scaffold. The method allows the creation of a library containing both drugs and prospective drug candidates without any priorly required knowledge on the pursued disease or molecular target. Two libraries having scaffolds derived from para-aminobenzoic acid and salicylic acid have exemplified the application of the chimera method. The validation of the method has been achieved through the high number of recognized drugs within the library, which exhibit in the same time a wide variety of therapeutic activities and interact with a broad spectrum of molecular targets. The drug-enriched chimera libraries are expected to provide a highly efficient access to novel drug candidates whose unspecified therapeutic effects should be further revealed through high-throughput screening.

4-Aminobenzoic Acid↗

PubMed2006

Evolution of audiometric pattern in Meniere's disease: long-term survey of 380 cases evaluated according to the 1995 guidelines of the American Academy of Otolaryngology-Head and Neck Surgery.

OBJECTIVES: Hearing loss in the early stages of Meniere's disease is characterized by a fluctuation in the audiometric pattern limited to the low frequencies, and then, during the disease's evolution, the hearing loss involves the medium and high frequencies. As far as the prevalence of different types of audiometric curves is concerned, there is no agreement among the various studies. The study of audiometric evolution in the course of the disease has been limited owing to the difficulties in following a relevant number of patients for a long period of time. The aim of the present study was to compare the auditory level and audiometric pattern evolution in a significant number of patients suffering from Meniere's disease who had undergone long-term follow-up (at least 10 years). METHODS: The study considered 380 patients with a confirmed diagnosis of Meniere's disease. The audiometric data were collected at the onset of the disease and after 5 and 10 years. Four patterns were considered: peak, rising, falling, and flat. Audiometric evolution analysis in four stages, defined by the guidelines of the American Academy of Otolaryngology-Head and Neck Surgery, was evaluated. RESULTS: At the onset, in 190 cases, the audiometric pattern was a peak curve, with fluctuation of the threshold in 68% of cases. The mean threshold shift for the 500 to 3000 Hz range was between 26 and 40 dB. After 5 years, a peak type (41.9%) or a flat type (42.9%) was observed; the pure-tone average (PTA) ranged between 26 and 40 dB in 47.9% and between 41 and 70 dB in 51.8% of cases. After 10 years, in most cases (57.9%), a flat curve was observed, and the PTA in 100% ranged between 41 and 70 dB. CONCLUSION: The most common audiometric pattern at the onset of the disease is the peak type; long-term transformation of the initial audiometric pattern into a flat curve has been confirmed. High-frequency involvement seemed to be related more to Meniere's disease duration than to the influence of aging on hearing loss.

Adult↗

PubMed2026

Adaptive Evolution of the PFK Gene Family in Chinese Longsnout Catfish, Leiocassis longirostris.

The Chinese longsnout catfish is a typical carnivorous fish with a relatively weak ability to utilize glucose. However, the genomic basis for its glucose metabolic adaptation remains unclear. In this study, we used comparative genomics methods to systematically analyze the evolutionary characteristics of glucose metabolism-related genes in the Chinese longsnout catfish, focusing on gene family evolution, patterns of expansion and contraction, and selective pressures. The results indicate that glucose metabolism-related genes have undergone significant reshaping during evolution. Genes involved in glucose digestion, absorption, and insulin signaling pathways demonstrate a tendency toward contraction, while those associated with protein and lipid metabolism exhibit expansion. This pattern is consistent with the species' long-term adaptation to a high-protein, high-fat diet. Comparative analysis further revealed that, compared to fish with different dietary habits, certain key genes involved in glycolysis in the Chinese longsnout catfish exhibit a reduction in copy number. Molecular evolutionary analysis showed that key genes involved in glycolysis and gluconeogenesis (including hexokinase 2 (hk2), phosphofructokinase, muscle/platelet (pfkm/p)) exhibit signs of accelerated evolution or positive selection. Notably, the PFK gene family exhibits complex evolutionary characteristics resulting from the combined effects of gene contraction, rapid evolution, and positive selection. In summary, this study reveals the genomic evolutionary basis for the glucose metabolic adaptation of the Chinese longsnout catfish and identifies the PFK gene family as a key candidate for elucidating its unique glucose metabolic characteristics.

Leiocassis longirostris↗